rs16924159

Positions:

• chr9-6229417-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033439.4(IL33):​c.-11-12267G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 152,100 control chromosomes in the GnomAD database, including 6,691 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (6691 hom., cov: 32)
• Consequence: IL33 NM_033439.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.144

Genes affected

IL33 (HGNC:16028): (interleukin 33) The protein encoded by this gene is a cytokine that binds to the IL1RL1/ST2 receptor. The encoded protein is involved in the maturation of Th2 cells and the activation of mast cells, basophils, eosinophils and natural killer cells. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2015]

LOC107987046 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL33	NM_033439.4	c.-11-12267G>A		intron_variant		ENST00000682010.1	NP_254274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL33	ENST00000682010.1	c.-11-12267G>A		intron_variant			NM_033439.4	ENSP00000507310.1
IL33	ENST00000417746.6	c.-11-12267G>A		intron_variant		2		ENSP00000394039.2

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42663 AN: 151982 Hom.: 6685 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.299

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.281 AC: 42671 AN: 152100 Hom.: 6691 Cov.: 32 AF XY: 0.284 AC XY: 21100 AN XY: 74332

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.348

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.274

Gnomad4 SAS AF: 0.358

Gnomad4 FIN AF: 0.315

Gnomad4 NFE AF: 0.332

Gnomad4 OTH AF: 0.299

Alfa AF: 0.325 Hom.: 12025

Bravo AF: 0.278

Asia WGS AF: 0.318 AC: 1107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.27

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs16924159; hg19: chr9-6229417; COSMIC: COSV70307198;